Interaction with SP1, but not binding to the E‐box motifs, is responsible for BHLHE40/DEC1‐induced transcriptional suppression of <i>CLDN1</i> and cell invasion in MCF‐7 cells

Zheng, Qin; Wang, Chen; Wang, Liang; Zhang, Di; Liu, Nan; Ming, Xiaocui; Zhou, Haitao; Guli, Qiere; Liu, Yang

doi:10.1002/mc.22829

Cited by 14 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BHLHE40 is expressed in a wide range of human tissues, and interacts with numerous nuclear proteins [31][32][33][34]. Apart from E-box binding, BHLHE40 was also shown to suppress transcription by binding to SP1 domains on target genes [35]. Targets of BHLHE40 regulated transcription are listed in Table 2.…”

Section: Introductionmentioning

confidence: 99%

Non-circadian aspects of BHLHE40 cellular function in cancer

2020

View full text Add to dashboard Cite

While many genes specifically act as oncogenes or tumor suppressors, others are tumor promoters or suppressors in a context-dependent manner. Here we will review the basic-helix-loop-helix (BHLH) protein BHLHE40, (also known as BHLHB2, STRA13, DEC1, or SHARP2) which is overexpressed in gastric, breast, and brain tumors; and downregulated in colorectal, esophageal, pancreatic and lung cancer. As a transcription factor, BHLHE40 is expressed in the nucleus, where it binds to target gene promoters containing the E-box hexanucleotide sequence, but can also be expressed in the cytoplasm, where it stabilizes cyclin E, preventing cyclin E-mediated DNA replication and cell cycle progression. In different organs BHLHE40 regulates different targets; hence may have different impacts on tumorigenesis. BHLHE40 promotes PI3K/Akt/ mTOR activation in breast cancer, activating tumor progression, but suppresses STAT1 expression in clear cell carcinoma, triggering tumor suppression. Target specificity likely depends on cooperation with other transcription factors. BHLHE40 is activated in lung and esophageal carcinoma by the tumor suppressor p53 inducing senescence and suppressing tumor growth, but is also activated under hypoxic conditions by HIF-1α in gastric cancer and hepatocellular carcinomas, stimulating tumor progression. Thus, BHLHE40 is a multi-functional protein that mediates the promotion or suppression of cancer in a context dependent manner.

show abstract

Section: Introductionmentioning

confidence: 99%

Non-circadian aspects of BHLHE40 cellular function in cancer

2020

View full text Add to dashboard Cite

show abstract

“…However, the underlying mechanisms are unclear. We previously reported that BHLHE40 regulates CLDN1 transcription and MCF‐7 cell invasion through binding with sp1 . In the current study, we aimed to explore whether BHLHE41 regulates cell invasion in the same manner as those found in the previous studies.…”

Section: Discussionmentioning

confidence: 66%

“…Members of this subfamily are involved in regulating various biological phenomena, such as circadian rhythm, cell proliferation, apoptosis, hypoxia and immune responses . A few recent studies have shown that BHLHE40 and BHLHE41 are involved in regulating cell invasion and metastasis . However, the underlying mechanisms are unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Plasmid pcDNA3.1, pcDNA3.1‐BHLHE40 and pcDNA3.1‐BHLHE41 were generous gifts from Prof. Kijima, and the efficiency was demonstrated in a previous study . The plasmid pcDNA3.1‐BHLHE40 was inserted with N‐His‐Flag‐tag, and the plasmid pcDNA3.1‐BHLHE41 was inserted with N‐His‐Myc‐tag as described previously . The MCF‐7 cells were seeded at a density of 1 × 10 5 cells per well (35 mm).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

BHLHE41 suppresses MCF‐7 cell invasion via MAPK/JNK pathway

Zhang

Zheng

Wang

et al. 2020

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

| 4001 wileyonlinelibrary.com/journal/jcmm | INTRODUC TI ONBasic helix-loop-helix family member e41 (BHLHE41, also known as SHARP1, DEC2 and BHLHB3) is mapped to human chromosome 12p12.1. It serves an important role in regulating cell differentiation, maintaining circadian rhythm, apoptosis, hypoxia and immune response. [1][2][3][4][5][6][7][8][9][10][11] The major functions of BHLHE41 are divided into two categories: circadian and non-circadian regulation. For the former, BHLHE41 protein re-enters the nucleus after transcription and translation and competes with CLOCK-BMAL1 heterodimer for E-Box element binding (through competitive inhibition). BHLHE41 functions as a suppressor of circadian rhythm regulation in this process. 11,12 For non-circadian regulation, BHLHE41 is implicated in multiple other pathways, such as BCR, notch, hypoxia, ERK/NF-kappaB and PI3K/Akt pathways. 3,6,8,[13][14][15] Dysregulation of BHLHE41 transcription levels has been characterized as a marker of the progression of several cancers. 8,[16][17][18][19][20][21][22][23] Abstract Deregulation of the basic helix-loop-helix family member e41 (BHLHE41) has been characterized as a marker of progression of several cancers. In this study, we aimed to explore the mechanism by which BHLHE41 regulates the invasion of breast cancer cells. BHLHE41 suppresses, whereas the silencing of BHLHE41 promotes tumour invasion of both MCF-7 and MDA-MB-231 cells. Meanwhile, BHLHE41 down-regulated the transcription and translation of SNAI1, SNAI2, VIM and CDH2, and up-regulated those of CLDN1, CLDN4 and CDH1. Reporter assay indicated that silencing of BHLHE41 dramatically activated the MAPK/JNK signalling pathway in MCF-7 cell line and the hypoxia signalling pathway in MDA-MB-231 cell line. Furthermore, silencing of BHLHE41 activated the MAPK/JNK signalling pathway by up-regulating phosphorylated JNK and failed to affect the expression of HIF-1 alpha in MCF-7 cells. After blocking the MAPK/JNK signalling pathway by specific inhibitor SP600125, silencing of BHLHE41 failed to promote tumour cell invasion. These results suggest that BHLHE41 facilitates MCF-7 cell invasion mainly via the activation of MAPK/ JNK signalling pathway. In conclusion, although BHLHE41 suppresses tumour invasion in MCF-7 and MDA-MB-231 cell lines, the specific regulatory mechanisms may be different. K E Y W O R D S BHLHE41, breast cancer, invasion, JNK signalling pathway, tight junction How to cite this article: Zhang D, Zheng Q, Wang C, Zhao N, Liu Y, Wang E. BHLHE41 suppresses MCF-7 cell invasion via MAPK/JNK pathway.

show abstract

“…Additionally, DEC1 has been reported to promote tumor progression, invasion and metastasis (13)(14)(15)(16). Previous studies have shown that DEC1 is associated with various types of human cancers, such as lung, gastric, liver and breast cancer (17)(18)(19)(20). Recently, Zhou et al (21) found that knockdown of cryptochrome circadian regulator 1 enhanced the proliferation and migration of osteosarcoma cells presenting downregulation of DEC1.…”

Section: Introductionmentioning

confidence: 99%

Effect of DEC1 on the proliferation, adhesion, invasion and epithelial‑mesenchymal transition of osteosarcoma cells

Peng

Yin

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

Differentiated embryonic chondrocyte-expressed gene 1 (DEC1) is associated with various types of human cancer; however, there is limited data regarding the functions of DEC1 in osteosarcoma. The present study aimed to examine the expression of DEC1 in human osteosarcoma tissues and cell lines. Furthermore, the effects of DEC1 on the proliferation, adhesion, invasion and epithelial-mesenchymal transition (EMT) of osteosarcoma cells were investigated. Using reverse transcription-quantitative PCR and western blot analysis, it was found that the expression levels of DEC1 were higher in human osteosarcoma tissues and osteosarcoma cell lines than in the controls. Both gain-and loss-of-function experiments suggested that DEC1 promotes the proliferation, adhesion and invasion of osteosarcoma cells in vitro, as determined by MTT, cell adhesion and cell invasion assays, respectively. Additionally, DEC1 was found to upregulate the mesenchymal markers N-cadherin and vimentin, whilst downregulating the epithelial marker E-cadherin. In conclusion, this present study showed increased expression levels of DEC1 in human osteosarcoma tissues and cell lines, and identified that DEC1 may exert its effect on osteosarcoma progression by promoting cell proliferation, adhesion and invasion. Furthermore, DEC1 was shown to have an inducible effect on EMT in osteosarcoma cell lines, thus contributing to the aggressiveness of osteosarcoma cells. This initial study indicated that DEC1 may serve as a novel molecular target for the treatment of osteosarcoma.

show abstract

Interaction with SP1, but not binding to the E‐box motifs, is responsible for BHLHE40/DEC1‐induced transcriptional suppression of CLDN1 and cell invasion in MCF‐7 cells

Cited by 14 publications

References 29 publications

Non-circadian aspects of BHLHE40 cellular function in cancer

Non-circadian aspects of BHLHE40 cellular function in cancer

BHLHE41 suppresses MCF‐7 cell invasion via MAPK/JNK pathway

Effect of DEC1 on the proliferation, adhesion, invasion and epithelial‑mesenchymal transition of osteosarcoma cells

Contact Info

Product

Resources

About